ABSTRACT
Figure 7. CSF levels of serotonin (5-HT) in PD patients (On and Off groups) and healthy controls.
CONCLUSIONS
One of the main problems during the many years of research on PD is to detect the disease early, since clinical diagnosis of PD will not appear until the DA depletion reaches a critical threshold in neostratum (Bernheimer et al, 1973). The disease is diagnosed on a clinical basis and there are no diagnostic tests. However, a positive response to levodopa administration is obvious and separates PD from other neurological disorders, which present with parkinsonism. New methods for early detection and monitoring of the disease progression to help the clinician in clinical diagnosis are important, particularly if future pharmacological treatments can halt further neurodegeneration and nerve cell death. One of the tools that have been used during the last few decades is to examine the patient's brain with positron emission tomography (PET). Combining this technique with analysis of biochemical, pathological and behavioral changes, more information on PD patients could be monitored. There is probably no single intracellular pathway that is responsible for the cell death of neurological diseases (Rothman et al, 1995). However, hyperactivity of the glutaminergic innervation, the associated activation of NMDA-receptor ion channels selective for Ca+2 and ensuing increase in the intracellular concentration of Ca+2 may contribute to the neurodegenerative process (Rothman et al, 1995). Besides, oxygen-free radicals, nitric oxide (NO) in particular, is thought to mediate NMDA-toxicity (Dawson et al, 1996). The evidence is accumulating to support the view that besides its beneficial actions, NO production from Arg could contribute and even initiate the cytotoxic effect and brain cell death. The mechanism by which NO kills brain cells is unknown;
however, free radical formation has been generally implicated in various forms of neurotoxicity (Whetsell, 1996). Our results do indicate increased accumulation of Arg and increased production of nitrite in both patient groups, and there is clear evidence that there is a linear correlation between the level of Glu and nitrite in PD patients. These results undoubtedly provide us with a possibility of understanding the interrelationship between different neurotransmitters in the brain as well as their distribution and functions. On the basis of these results on degenerative disorders, the role of various neurotransmitters, and the role of free radical NO must be clearly defined in order to develop effective drug therapy. If such a scenario indeed occurs, then a variety of therapeutic approach are possible. This includes glutamate release inhibitors, EAA antagonists, agents to improve mitochondrial function, free radical scavengers and neurotropic factors.
